Czubayko, U. | bioRxiv Science

bioRxiv2025

Acute obstructive uropathy in male C57Bl/6 mice after general anesthesia with fentanyl, midazolam and medetomidine

The selective alpha-2 adrenoreceptor agonist medetomidine is commonly used as a component of combination solutions for general anesthesia in rodents and small animals. However, it has also been reported to increase the risk of obstructive uropathy in male mice. Here we report that in a recent cohort of mice undergoing two sequential surgical procedures using the anesthetic combination of fentanyl, midazolam and medetomidine (FMM) for general anesthesia, 60% of the male mice developed severe obstructive uropathy within 48 hours of the second surgery. We also report one case of an older male mouse developing severe obstructive uropathy after a single general anesthesia with FMM. In a subsequent pilot study involving five male mice undergoing similar surgical procedures, also with two sequential surgeries, but using xylazine as the alpha-2 adrenoreceptor agonist in the narcotic combination, none of the animals developed obstructive uropathy in the post-operative period or thereafter. We suggest that replacement of medetomidine with xylazine should be considered for general anesthesia in male mice undergoing multiple successive anesthesia events or in for procedures in older males.

pathology↗

bioRxiv2018

Accurate action potential inference from a calcium sensor protein through biophysical modeling

Multiphoton imaging of genetically encoded calcium indicators is routinely used to report activity from populations of spatially resolved neurons in vivo. However, since the relationship between fluorescence and action potentials (APs) is nonlinear and varies over neurons, quantitatively inferring AP discharge is problematic. To address this we developed a biophysical model of calcium binding kinetics for the indicator GCaMP6s that accurately describes AP-evoked fluorescence changes in vivo. The models physical interpretation allowed the same parameters to describe GCaMP6s binding kinetics for both in vitro binding assays and in vivo imaging. Using this model, we developed an algorithm to infer APs from fluorescence and measured its accuracy with cell-attached electrical recordings. This approach consistently inferred more accurate AP counts and times than alternative methods for firing rates from 0 to >20 Hz, while requiring less training data. These results demonstrate the utility of quantitative, biophysically grounded models for complex biological data.

neuroscience↗